Knockdown of end-binding protein 1 induces apoptosis in radioresistant A549 lung cancer cells via p38 kinase-dependent COX-2 upregulation.

Abstract

The role of end-binding protein 1 (EB1) in lung cancer tumorigenesis and radiotherapy remains poorly understood. In the present study, we observed that EB1 was highly expressed in lung tumor tissues compared with normal non-tumor tissues based on immunohistochemical analysis of lung cancer tissue samples obtained from human tissue microarrays. EB1 was also highly overexpressed in radioresistant lung and cervical cancer cells, which exhibited increased cell death after EB1 silencing. The cytotoxicity induced by EB1 gene knockdown was due to the activation and generation of reactive oxygen species by p38 mitogen-activated protein kinase. Notably, this signaling cascade, however not nuclear factor-κB-mediated signaling, induced the expression of cyclooxygenase-2, a key effector of apoptotic death. Our results provided new molecular evidence supporting the use of EB1 as a novel target in lung cancer therapy, especially in the case of radioresistance.

• Authors: Jeong-Hwa Baek, Ji-Hye Yim, Jie-Young Song, Hong-Duck Um, Jong Kuk Park, In-Chul Park, Jae-Sung Kim, Chang-Woo Lee, Eun-Hee Hong, Eun Ho Kim, Sang-Gu Hwang
• Journal: Oncology reports (Oncol Rep) Vol. 39 Issue 4 Pg. 1565-1572 (Apr 2018) ISSN: 1791-2431 [Electronic] Greece
• PMID: 29484424 (Publication Type: Journal Article)

Chemical References

• MAPRE1 protein, human
• Microtubule-Associated Proteins
• Reactive Oxygen Species
• Cyclooxygenase 2
• PTGS2 protein, human
• p38 Mitogen-Activated Protein Kinases

Topics

• A549 Cells
• Apoptosis (genetics)
• Cell Proliferation (genetics)
• Cyclooxygenase 2 (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Lung Neoplasms (genetics, pathology)
• MAP Kinase Signaling System (genetics)
• Microtubule-Associated Proteins (genetics)
• Reactive Oxygen Species (metabolism)
• Tissue Array Analysis
• p38 Mitogen-Activated Protein Kinases (genetics)